Impact of ITV/GTV Ratio on Local Failure in Early Stage Non-Small Cell Lung Cancer Patients Receiving Stereotactic Ablative Radiation Therapy

Abstract

The free-breathing internal target volume (ITV) approach is a popular motion management strategy that covers the gross tumor volume (GTV) throughout respiration during stereotactic ablative radiation therapy (SABR) for lung cancer. A large ITV/GTV ratio suggests significant tumor motion during the respiratory cycle relative to the tumor's volume which may result in increased risk of geographic miss and local failure. We hypothesized that higher ITV/GTV ratio is associated with higher rates of local failure following SABR for early stage non-small cell lung cancer (NSCLC).Patients with early stage NSCLC archived in a prospective, IRB-approved tumor registry were identified and reviewed for treatment failure following SABR. All SABR plans utilized the ITV approach with a free-breathing 4DCT to account for tumor motion. Treatment failure was based on two criteria: persistent tumor growth on CT and evidence of tumor viability (confirmed by biopsy or FDG PET revealing uptake consistent with malignancy). Failure was categorized as primary at the treatment site, lobar if within the treated lobe (excluding primary site), or local if either primary or lobar. GTV, ITV, target min/mean/max doses, histology, T stage, lobe involved, and the use of abdominal compression were recorded. ITV/GTV ratio was calculated for each case. The effect of ITV/GTV on local failure was assessed using the Cox proportional hazard model. The effects of ITV/GTV on primary and lobar failure were assessed using the Kaplan-Meier method and log-rank test. Significance was set at P < 0.05 for each comparison.A total of 305 patients with complete dosimetric data were treated from 10/2005 to 3/2015 with a median follow up of 19.5 months (range, 0-168 months). Local, primary, and lobar failure were observed in 12.8%, 6.2%, and 6.6% of patients, respectively. No dosimetric or clinical factor, including the ITV/GTV ratio, was significantly associated with local failure on univariate Cox analysis. ITV/GTV ratio > 1.37 (median value) demonstrated a trend toward longer failure-free interval at the primary site (22.2 vs 18.1 months, P = 0.08) while no trend was observed between ITV/GTV ratio and lobar failure.In this cohort, the ITV/GTV ratio was not significantly associated with local failure; however, ITV/GTV ratio > 1.37 demonstrated a trend toward longer failure-free interval at the primary site on subgroup analysis. This is the inverse of our initial hypothesis and suggests that capturing the entire motion envelope within the free-breathing ITV may be important for optimizing primary tumor control. Further investigation of the ITV/GTV ratio and its association with local failure is warranted in a larger cohort with a greater number of failures to allow for more comprehensive analysis of the primary and lobar components.